Polyglutamine expanded ataxin-7 alters NOX1 activity and cellular metabolism
2013 (English)In: Article in journal (Refereed) Submitted
Spinocerebellar ataxia type 7 (SCA7) is one of nine inherited neurodegenerative disorders caused by polyglutamine (polyQ) expansions. Common pathogenic mechanisms, including oxidative stress and metabolic dysfunction, have been implicated in polyQ disease. However, the exact toxic mechanism(s) is still unclear. We have previously demonstrated that expression of the SCA7 disease protein, ATXN7, results in oxidative stress and toxicity via activation of ROS-producing NADPH oxidase (NOX) enzymes. In this study, we show that mutant ATXN7 specifically up-regulates and activates the NOX1 family member. Furthermore, we show that the increased NOX1 activity is linked with a metabolic shift, similar to the Warburg effect, and reduced energy levels. Reduction of the NOX1-mediated ROS production reverse the metabolic shift and rescue the ATXN7 induced toxicity. These data suggest that NOX1-mediated metabolic alterations and energy deficit could play a role in SCA7 pathology and possibly in other polyQ diseases.
Place, publisher, year, edition, pages
neurodegeneration, polyglutamine, NADPH oxidase, metabolism
Research subject Neurochemistry with Molecular Neurobiology
IdentifiersURN: urn:nbn:se:su:diva-94133OAI: oai:DiVA.org:su-94133DiVA: diva2:651889
FunderSwedish Research Council, K2010-68X-21449-01-1